DOCSLIB.ORG

European Medicines Agency Recommends Orphan Drug Designation for Relacorilant to Treat Patients with Cushing’S Syndrome

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
European Medicines Agency Recommends Orphan Drug Designation for Relacorilant to Treat Patients with Cushing’S Syndrome European Medicines Agency Recommends Orphan Drug Designation for Relacorilant to Treat Patients with Cushing’s Syndrome May 2, 2019 MENLO PARK, Calif., May 02, 2019 (GLOBE NEWSWIRE) -- Corcept Therapeutics Incorporated (NASDAQ: CORT), a commercial-stage company engaged in the discovery and development of drugs to treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of the stress hormone cortisol, today announced that the European Medicines Agency Committee for Orphan Medicinal Products (COMP) has issued a positive opinion recommending the approval of orphan drug designation for Corcept’s proprietary, selective cortisol modulator, relacorilant, for the treatment of Cushing’s syndrome. The European Commission is expected to adopt the COMP’s recommendation in May 2019. Orphan drug designation in the European Union (EU) provides regulatory and financial incentives for companies to develop and market therapies to treat serious disorders affecting no more than five in 10,000 persons in the EU, including ten-year marketing exclusivity in the EU upon approval, eligibility for protocol assistance, reduced fees and access to the EU’s centralized marketing authorization procedure. To be considered for orphan designation in the EU, there must be plausible evidence of a drug candidate’s efficacy and of its potential to confer significant clinical benefit compared to already-approved treatments. The COMP letter states, “The sponsor has provided clinical data that demonstrate that the product can reduce blood pressure and improve control of hyperglycaemia in patients who were not adequately managed by currently authorised products. The Committee considered that this constitutes a clinically relevant advantage.” The medications ketoconazole, metyropone and pasireotide are approved in the EU for the treatment of one or more aetologies of Cushing’s syndrome. Corcept based its submission on data from relacorilant’s Phase 2 trial, in which patients demonstrated improvements in the primary endpoints of glucose control and hypertension, and in a variety of secondary endpoints, including weight loss, liver function, coagulopathy, cognition, mood, insulin resistance, and quality of life. Relacorilant was well-tolerated, with the most common treatment-emergent adverse events being those associated with reduction in excess cortisol activity – headache, nausea, back pain and edema – that usually resolve with continued treatment. Because relacorilant, unlike Corcept’s FDA-approved cortisol modulator, Korlym®, does not bind to the progesterone receptor, patients did not experience vaginal bleeding caused by uterine thickening, a frequently-reported adverse event of Korlym. There were also no cases of drug-induced hypokalemia (low potassium), a leading cause of Korlym discontinuation. Relacorilant’s Phase 3 GRACE trial is underway and is expected to enroll 130 patients at 60 sites in the United States, Canada, Europe and Israel. The United States Food and Drug Administration granted relacorilant orphan drug status for Cushing’s syndrome in October 2018. Cushing’s Syndrome Hypercortisolism, often referred to as Cushing’s syndrome, is caused by excessive activity of the hormone cortisol. Endogenous Cushing’s syndrome is an orphan disease that most often affects adults aged 20-50. In the United States, an estimated 20,000 patients have Cushing’s syndrome, with about 3,000 new patients being diagnosed each year. Symptoms vary, but most people experience one or more of the following manifestations: high blood sugar, diabetes, high blood pressure, upper-body obesity, rounded face, increased fat around the neck, thinning arms and legs, severe fatigue and weak muscles. Irritability, anxiety, cognitive disturbances and depression are also common. Hypercortisolism can affect every organ system in the body and can be lethal if not treated effectively. Corcept Therapeutics Incorporated Corcept is a commercial-stage company engaged in the discovery and development of drugs that treat severe metabolic, oncologic and psychiatric disorders by modulating the effects of the stress hormone cortisol. Corcept’s approved product, Korlym ®, was the first FDA-approved treatment for patients with Cushing’s syndrome. Korlym modulates the activity of cortisol at the glucocorticoid receptor, one of the two receptors to which cortisol binds. Corcept has discovered a large portfolio of proprietary compounds that selectively modulate the effects of cortisol but not progesterone. Corcept owns extensive United States and foreign intellectual property covering the composition of its selective cortisol modulators and in the use of cortisol modulators, including Korlym, to treat a wide variety of serious disorders. Forward-Looking Statements Statements in this press release, other than statements of historical fact, are forward-looking statements, which are based on our current plans and expectations and are subject to risks and uncertainties that might cause actual results to differ materially from those such statements express or imply. These risks and uncertainties include, but are not limited to, our ability to generate sufficient revenue to fund our commercial operations and development programs; the availability of competing treatments, including generic versions of Korlym; our ability to obtain acceptable prices or adequate insurance coverage and reimbursement for Korlym; and risks related to the development of our product candidates, including regulatory approvals, mandates, oversight and other requirements. These and other risks are set forth in our U.S. Securities and Exchange Commission (SEC) filings, which are available at our website and the SEC’s website. In this press release, forward-looking statements include those concerning expectations that the European Commission will adopt the COMP’s recommendation in May 2019; the regulatory and financial incentives accompanying orphan drug designation; the progress, timing, design and results of our development programs, including the GRACE trial; and the scope and protective power of our intellectual property. We disclaim any intention or duty to update forward-looking statements made in this press release. CONTACT: Christopher S. James, MD Director, Investor Relations Corcept Therapeutics 650-684-8725 [email protected] www.corcept.com Source: Corcept Therapeutics Incorporated.
Load more

Recommended publications
  • Efficacy and Safety of the Selective Glucocorticoid Receptor Modulator
    Efficacy and Safety of the Selective Glucocorticoid Receptor Modulator, Relacorilant (up to 400 mg/day), in Patients With Endogenous Hypercortisolism: Results From an Open-Label Phase 2 Study Rosario Pivonello, MD, PhD1; Atil Y. Kargi, MD2; Noel Ellison, MS3; Andreas Moraitis, MD4; Massimo Terzolo, MD5 1Università Federico II di Napoli, Naples, Italy; 2University of Miami Miller School of Medicine, Miami, FL, USA; 3Trialwise, Inc, Houston, TX, USA; 4Corcept Therapeutics, Menlo Park, CA, USA; 5Internal Medicine 1 - San Luigi Gonzaga Hospital, University of Turin, Orbassano, Italy INTRODUCTION EFFICACY ANALYSES Table 5. Summary of Responder Analysis in Patients at Last SAFETY Relacorilant is a highly selective glucocorticoid receptor modulator under Key efficacy assessments were the evaluation of blood pressure in the Observation Table 7 shows frequency of TEAEs; all were categorized as ≤Grade 3 in hypertensive subgroup and glucose tolerance in the impaired glucose severity investigation for the treatment of all etiologies of endogenous Cushing Low-Dose Group High-Dose Group tolerance (IGT)/type 2 diabetes mellitus (T2DM) subgroup Five serious TEAEs were reported in 4 patients in the high-dose group syndrome (CS) Responder, n/N (%) Responder, n/N (%) o Relacorilant reduces the effects of cortisol, but unlike mifepristone, does o Response in hypertension defined as a decrease of ≥5 mmHg in either (pilonidal cyst, myopathy, polyneuropathy, myocardial infarction, and not bind to progesterone receptors (Table 1)1 mean systolic blood pressure (SBP) or diastolic blood pressure (DBP) from HTN 5/12 (41.67) 7/11 (63.64) hypertension) baseline No drug-induced cases of hypokalemia or abnormal vaginal bleeding were IGT/T2DM 2/13 (15.38) 6/12 (50.00) o Response in IGT/T2DM defined by one of the following: noted Table 1.
    [Show full text]
  • Recurrence After Pituitary Surgery in Adult Cushing's Disease: a Systematic Review on Diagnosis and Treatment
    Endocrine https://doi.org/10.1007/s12020-020-02432-z REVIEW Recurrence after pituitary surgery in adult Cushing’s disease: a systematic review on diagnosis and treatment 1 1 1 1 2 Leah T. Braun ● German Rubinstein ● Stephanie Zopp ● Frederick Vogel ● Christine Schmid-Tannwald ● 3 4 5 1 Montserrat Pazos Escudero ● Jürgen Honegger ● Roland Ladurner ● Martin Reincke Received: 13 May 2020 / Accepted: 20 July 2020 © The Author(s) 2020 Abstract Purpose Recurrence after pituitary surgery in Cushing’s disease (CD) is a common problem ranging from 5% (minimum) to 50% (maximum) after initially successful surgery, respectively. In this review, we give an overview of the current literature regarding prevalence, diagnosis, and therapeutic options of recurrent CD. Methods We systematically screened the literature regarding recurrent and persistent Cushing’s disease using the MESH term Cushing’s disease and recurrence. Of 717 results in PubMed, all manuscripts in English and German published between 1980 and April 2020 were screened. Case reports, comments, publications focusing on pediatric CD or CD in 1234567890();,: 1234567890();,: veterinary disciplines or studies with very small sample size (patient number < 10) were excluded. Also, papers on CD in pregnancy were not included in this review. Results and conclusions Because of the high incidence of recurrence in CD, annual clinical and biochemical follow-up is paramount. 50% of recurrences occur during the first 50 months after first surgery. In case of recurrence, treatment options include second surgery, pituitary radiation, targeted medical therapy to control hypercortisolism, and bilateral adrena- lectomy. Success rates of all these treatment options vary between 25 (some of the medical therapy) and 100% (bilateral adrenalectomy).
    [Show full text]
  • Hypokalemia Associated with Mifepristone Use in the Treatment of Cushing’S Syndrome
    ID: 19-0064 -19-0064 S Katta and others Mifepristone toxicity ID: 19-0064; November 2019 DOI: 10.1530/EDM-19-0064 Hypokalemia associated with mifepristone use in the treatment of Cushing’s syndrome Sai Katta1, Amos Lal1, Jhansi Lakshmi Maradana1, Pruthvi Raj Velamala1 and Nitin Trivedi2 Correspondence should be addressed 1Department of Internal Medicine, Saint Vincent Hospital at Worcester Medical Center, Worcester, Massachusetts, to S Katta USA and 2Department of Endocrinology, Diabetes, and Metabolism, Saint Vincent Hospital at Worcester Medical Email Center, Worcester, Massachusetts, USA [email protected] Summary Mifepristone is a promising option for the management of hypercortisolism associated with hyperglycemia. However, its use may result in serious electrolyte imbalances, especially during dose escalation. In our patient with adrenocorticotropic hormone-independent macro-nodular adrenal hyperplasia, unilateral adrenalectomy resulted in biochemical and clinical improvement, but subclinical hypercortisolism persisted following adrenalectomy. She was started on mifepristone. Unfortunately, she missed her follow-up appointments following dosage escalation and required hospitalization at an intensive care level for severe refractory hypokalemia. Learning points: • Mifepristone,apotentantagonistofglucocorticoidreceptors,hasahighriskofadrenalinsufficiency,despitehigh cortisol levels. • Mifepristoneisassociatedwithhypokalemiaduetospill-overeffectofcortisolonunopposedmineralocorticoid receptors. • Given the lack of a biochemical parameter
    [Show full text]
  • Study Protocol Cort125134-451
    Title: Phase 2 Study of the Safety and Efficacy of CORT125134 in the Treatment of Endogenous Cushing’s Syndrome NCT number: NCT02804750 Date: 15 January 2018 CLINICAL STUDY PROTOCOL CORT125134-451 Protocol Title Phase 2 Study of the Safety and Efficacy of CORT125134 in the Treatment of Endogenous Cushing’s Syndrome Study Phase 2 IND Number 128625 Investigational Product CORT125134 International Relacorilant Nonproprietary Name Medical Monitor Clinical Trial Lead Sponsor Corcept Therapeutics Incorporated 149 Commonwealth Drive Menlo Park, California 94025 US +1 (650) 327-3270 Version 7.0 Date Final 15 January 2018 Good Clinical Practice Statement This study will be conducted in accordance with Good Clinical Practice (GCP) as defined in International Conference on Harmonisation (ICH) guidelines and US Code of Federal Regulations Title 21, Parts 11, 50, 54, 56, 312, and Title 45 Parts 46, 160 and 164; the ICH document “Guidance for Industry – E6 Good Clinical Practice: Consolidated Guidance”; the EU Directives 2001/20/EC and 2005/28/EC; the Declaration of Helsinki (version as currently endorsed by the European Medicines Evaluation Agency and the United States Food and Drug Administration [FDA], 1989); Institutional Review Board (IRB) Guidelines; and applicable local legal and regulatory requirements. Confidentiality Statement This document contains information which is the confidential and proprietary property of Corcept Therapeutics. Any use, distribution, or disclosure without the prior written consent of Corcept Therapeutics is strictly prohibited except to the extent required under applicable laws or regulations. Persons to whom the information is disclosed must be informed that the information is confidential and may not be further disclosed by them.
    [Show full text]
  • Rxoutlook® 3Rd Quarter 2020
    ® RxOutlook 3rd Quarter 2020 optum.com/optumrx a RxOutlook 3rd Quarter 2020 In this edition of RxOutlook, we highlight 13 key pipeline drugs with potential to launch by the end of the fourth quarter of 2020. In this list of drugs, we continue to see an emphasis on rare diseases. Indeed, almost half of the drugs we review here have FDA Orphan Drug Designation for a rare, or ultra-rare condition. However, this emphasis on rare diseases is also balanced by several drugs for more “mainstream” conditions such as attention deficit hyperactivity disorder, hypercholesterolemia, and osteoarthritis. Seven are delivered via the oral route of administration and three of these are particularly notable because they are the first oral option in their respective categories. Berotralstat is the first oral treatment for hereditary angioedema, relugolix is the first oral gonadotropin releasing hormone receptor antagonist for prostate cancer, and roxadustat is the first oral treatment for anemia of chronic kidney disease. Two drugs this list use RNA-based mechanisms to dampen or “silence” genetic signaling in order to correct an underlying genetic condition: Lumasiran for primary hyperoxaluria type 1, and inclisiran for atherosclerosis and familial hypercholesterolemia. These agents can be given every 3 or 6 months and fill a space between more traditional chronic maintenance drugs the require daily administration and gene therapies that require one time dosing for long term (and possible life-long) benefits. Key pipeline drugs with FDA approval decisions
    [Show full text]
  • Glucocorticoid Receptor Antagonism Promotes Apoptosis in Solid Tumor Cells
    www.oncotarget.com Oncotarget, 2021, Vol. 12, (No. 13), pp: 1243-1255 Research Paper Glucocorticoid receptor antagonism promotes apoptosis in solid tumor cells Andrew E. Greenstein1 and Hazel J. Hunt1 1Corcept Therapeutics, Menlo Park, CA, USA Correspondence to: Andrew E. Greenstein, email: [email protected] Keywords: glucocorticoid; tumors; apoptosis; chemotherapy; drug resistance Received: March 28, 2021 Accepted: June 02, 2021 Published: June 22, 2021 Copyright: © 2021 Greenstein and Hunt. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Background: Resistance to antiproliferative chemotherapies remains a significant challenge in the care of patients with solid tumors. Glucocorticoids, including endogenous cortisol, have been shown to induce pro-survival pathways in epithelial tumor cells. While pro-apoptotic effects of glucocorticoid receptor (GR) antagonism have been demonstrated under select conditions, the breadth and nature of these effects have not been fully established. Materials and Methods: To guide studies in cancer patients, relacorilant, an investigational selective GR modulator (SGRM) that antagonizes cortisol activity, was assessed in various tumor types, with multiple cytotoxic combination partners, and in the presence of physiological cortisol concentrations. Results: In the MIA PaCa-2 cell line, paclitaxel-driven apoptosis was blunted by cortisol and restored by relacorilant. In the OVCAR5 cell line, relacorilant improved the efficacy of paclitaxel and the potency of platinum agents. A screen to identify optimal combination partners for relacorilant showed that microtubule- targeted agents consistently benefited from combination with relacorilant.
    [Show full text]
  • Public Summary of Opinion on Orphan Designation Relacorilant for the Treatment of Cushing’S Syndrome
    2 August 2019 EMADOC-628903358-935 Public summary of opinion on orphan designation Relacorilant for the treatment of Cushing’s syndrome On 29 May 2019, orphan designation (EU/3/19/2164) was granted by the European Commission to Granzer Regulatory Consulting & Services, Germany, for relacorilant for the treatment of Cushing’s syndrome. What is Cushing’s syndrome? Cushing's syndrome is a disease characterised by an excess of the hormone cortisol in the blood. It is usually caused by a tumour of the pituitary gland (a gland located at the base of the brain) that produces large amounts of adrenocorticotropic hormone (ACTH), which in turn stimulates the production of excess cortisol from the adrenal glands, which are situated above the kidney. Some patients with the syndrome have other kinds of tumours that produce ACTH, or tumours that produce excess cortisol directly. Symptoms of Cushing's syndrome include weight gain affecting the face and torso but not the limbs, growth of fat above the collar bone and the back of the neck, a roundish face, easy bruising, excessive growth of coarse hair on the face, weakening of the muscles and bones, depression, diabetes and high blood pressure. Cushing's syndrome is a severe disease that is long lasting and may be life threatening because of its complications, including diabetes, high blood pressure and mental problems. What is the estimated number of patients affected by Cushing’s syndrome? At the time of designation, Cushing’s syndrome affected approximately 0.6 in 10,000 people in the European Union (EU). This was equivalent to a total of around 31,000 people*, and is below the ceiling for orphan designation, which is 5 people in 10,000.
    [Show full text]
  • Lääkeaineiden Yleisnimet (INN-Nimet) 31.12.2019
    Lääkealan turvallisuus- ja kehittämiskeskus Säkerhets- och utvecklingscentret för läkemedelsområdet Finnish Medicines Agency Lääkeaineiden yleisnimet (INN-nimet) 31.12.
    [Show full text]
  • Fixing the Broken Clock in Adrenal Disorders: Focus on Glucocorticoids and Chronotherapy
    246 2 Journal of M Minnetti et al. Using hormones and drugs as 246:2 R13–R31 Endocrinology entrainers REVIEW Fixing the broken clock in adrenal disorders: focus on glucocorticoids and chronotherapy Marianna Minnetti1, Valeria Hasenmajer1, Riccardo Pofi1, Mary Anna Venneri1, Krystallenia I Alexandraki2 and Andrea M Isidori 1 1Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy 2Endocrine Unit, 1st Department of Propaedeutic Medicine, Laiko University Hospital, Medical School, National and Kapodistrian University of Athens, Athens, Greece Correspondence should be addressed to A M Isidori: [email protected] This article is based, in part, on a symposium presented at the 21st European Conference of Endocrinology, 18–21 May 2019, Lyon, France Abstract The circadian rhythm derives from the integration of many signals that shape the Key Words expression of clock-related genes in a 24-h cycle. Biological tasks, including cell f adrenal hormomes proliferation, differentiation, energy storage, and immune regulation, are preferentially f corticosteroids confined to specific periods. A gating system, supervised by the central and peripheral f circadian rhythms clocks, coordinates the endogenous and exogenous signals and prepares for transition f glucose metabolism to activities confined to periods of light or darkness. The fluctuations of cortisol and its f HPA axis (hypothalamus- receptor are crucial in modulating these signals. Glucocorticoids and the autonomous pituitary-adrenal) nervous system act as a bridge between the suprachiasmatic master clock and almost all peripheral clocks. Additional peripheral synchronizing mechanisms including metabolic fluxes and cytokines stabilize the network. The pacemaker is amplified by peaks and troughs in cortisol and their response to food, activity, and inflammation.
    [Show full text]
  • Annexes to the 2019 Annual Report of the European Medicines Agency
    Annexes – 2019 annual report of the European Medicines Agency Annex 1 – Members of the Management Board ............................................................................. 2 Annex 2 - Members of the Committee for Medicinal Products for Human Use .................................... 4 Annex 3 – Members of the Pharmacovigilance Risk Assessment Committee ...................................... 6 Annex 4 – Members of the Committee for Medicinal Products for Veterinary Use ............................... 8 Annex 5 – Members of the Committee on Orphan Medicinal Products ............................................ 10 Annex 6 – Members of the Committee on Herbal Medicinal Products .............................................. 11 Annex 7 – Committee for Advanced Therapies ............................................................................ 13 Annex 8 – Members of the Paediatric Committee ........................................................................ 15 Annex 9 – Working parties and working groups .......................................................................... 17 Annex 10 – CHMP opinions on initial evaluations and extensions of therapeutic indication in 2019 .... 23 Annex 11 – Guidelines and concept papers adopted by CHMP ....................................................... 24 Annex 12 – CVMP opinions on medicinal products for veterinary use in 2019 .................................. 27 Annex 13 – Guidelines and concept papers adopted by CVMP in 2019 ............................................ 36 Annex
    [Show full text]
  • PDF Download
    Published online: 2019-12-20 Review Updates in the Medical Treatment of Pituitary Adenomas Authors Monica Livia Gheorghiu1, Francesca Negreanu2, Maria Fleseriu2 Affiliations ABSTRACT 1 CI Parhon National Institute of Endocrinology, Carol Davila Pituitary adenomas represent approximately 15 % of brain tu- University of Medicine and Pharmacy, Bucharest, Romania mors; incidence is significantly on the increase due to wides- 2 Northwest Pituitary Center, and Departments of Medicine pread use of magnetic resonance imaging. Surgery remains (Endocrinology) and Neurological Surgery, Oregon Health the first-line treatment for most tumors overall. The role of & Science University, Portland, United States dopaminergic agonists (DAs) and somatostatin receptor ligan- ds (SRLs) in the treatment of pituitary adenomas is quite well Key words established for prolactinomas and growth hormone (GH) ex- prolactinoma, somatostatin receptor ligands, non functio- cess. However, over the last decade new multi-receptor binding ning pituitary adenomas, glucocorticoid receptor blockade, SRLs are increasingly used for treatment of acromegaly and adrenal steroidogenesis inhibitors, Cushing’s disease, Cushing’s disease. SRLs/DA chimeric compounds seem to have acromegaly, pituitary adenoma enhanced potency and efficacy when compared to that of in- dividual SRLs or DA receptor agonists according to preclinical received 03.10.2019 data. However, following negative results, more research is accepted 13.11.2019 needed to determine if this interesting mechanism will trans- late into positive clinical effects for acromegaly patients. Fur- Bibliography thermore, new agents that block adrenal steroidogenesis have DOI https://doi.org/10.1055/a-1066-4592 been developed in phase III clinical trials for Cushing’s disease Published online: 20.12.2019 and several new compounds working at the pituitary level and/ Horm Metab Res 2020; 52: 8–24 or blocking the glucocorticoid receptor are also in develop- © Georg Thieme Verlag KG Stuttgart · New York ment.
    [Show full text]
  • Summer 2018 Cushing’S Newsletter
    Cushing’s Support & Research Foundation Summer 2018 cushing’s newsletter THE SCIENCE ISSUE our meetings between March and May of this year provided a treasure chest of new research about Cushing’s, Adrenal Insufficiency, and everything in be- F tween. In March we exhibited and attended sessions at ENDO2018, the En- docrine Society’s annual meeting in Chicago. Later that month we attended Adrenal Insufficiency United’s first-ever conference in Kansas City, MO and met up with about a dozen other Cushing’s patients including Associate Board Member Danielle Reszenski Inside this issue and Marie Conley of the Conley Cushing’s Disease Fund. In the middle of May we had News and Updates ............ 3 representatives on two continents attending presentations and talking to attendees: at the American Association of Clinical Endocrinologists (AACE) conference in Boston and Articles. 9 the European Society of Endocrinology (ECE) annual meeting in Barcelona, Spain. It is Adrenal Insufficiency ......... 13 exciting to see all the emerging breakthroughs regarding issues of the Endocrine System. Doctor’s Answers ............. 16 We returned with notes, slides, memories of conversations, and a lot of anticipation Research Summaries. 18 about sharing everything with our membership. Our goal with this issue was to translate the knowledge that we absorbed into a language that makes sense. When specific num- Clinical Trials ................. 20 bers, percentages, or details are listed, the data came directly from the doctors’ pre- In Memoriam ................. 22 sentations. Articles and research are cited when used. We hope that we are accurately communicating the volume of work being done that directly affects our community.
    [Show full text]